Effect of testosterone on the rat adrenal cortical 11β-hydroxylation system

Abstract

The influence of testosterone on the adrenal mitochondrial steroid hydroxylation system was investigated in the female Sprague-Dawley rat. After the injection of animals with testosterone for 10 days, it was possible to demonstrate impairment of progesterone metabolism in adrenal homogenates. The formation of corticosterone and 18-hydroxy-11-deoxycorticosterone was lower than in controls and there was an accumulation of 11-deoxycorticosterone (DOC). Adrenal mitochondria isolated from testosterone-treated rats showed low rates of conversion of DOC-4- 14C to corticosterone and 18-hydroxy-DOC, confirming the low activity of steroid 11β- and 18-hydroxylases. Rates of corticosterone formation from unlabeled DOC were also lower in adrenal mitochondria from testosterone-treated animals. Accompanying these low steroid hydroxylation activities in isolated mitochondria were decreased levels of adrenal mitochondrial cytochrome P-450. In addition, spectral studies revealed that the DOC-induced spectral change was considerably less in the adrenal mitochondria from testosterone-treated rats. The results described in this communication are consistent with the concept that, after injection into the rat, testosterone reaches the adrenal cortex and there interacts with the mitochondrial cytochrome P-450 in such a way that the natural substrate, DOC, is less able to be bound and hydroxylated. This hypothesis was confirmed by the addition of testosterone to rat adrenal mitochondria in vitro and the observation of inhibition of both DOC-induced spectral changes and steroid hydroxylation.